Targeted liposomes encapsulated iridium(III) compound greatly enhance anticancer efficacy and induce cell death via ferroptosis on HepG2 cells.

Autor: Chen J; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China., Li W; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China., Li G; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China., Liu X; Jiaying University, Meizhou, 514031, PR China., Huang C; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China., Nie H; Jiaying University, Meizhou, 514031, PR China. Electronic address: niehua@jyu.edu.cn., Liang L; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China., Wang Y; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China., Liu Y; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China. Electronic address: lyjche@gdpu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2024 Feb 05; Vol. 265, pp. 116078. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1016/j.ejmech.2023.116078
Abstrakt: In this study, ligands 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (PIP), 2-(2-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (NPIP), 2-(2-nitronaphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NNIP) and their iridium(III) metal compounds [Ir(ppy) 2 (PIP)](PF 6 ) (ppy = 2-phenylpyridine, 1a), [Ir(ppy) 2 (NPIP)](PF 6 ) (1b), [Ir(ppy) 2 (NNIP)](PF 6 ) (1c) were designed and synthesized. The anti-cancer activities of 1a, 1b and 1c on BEL-7402, HepG2, SK-Hep1 and non-cancer LO2 were detected using MTT method. 1a shows moderate, 1b and 1c display low or no anti-cancer activities. To elevate the anti-cancer effectiveness, encapsulating the compounds 1a, 1b and 1c into the ordinary or targeted liposomes to produce 1alip, 1blip, 1clip, or targeted 1aTlip, 1bTlip and 1cTlip. The IC 50 values of 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip against HepG2 cells are 7.9 ± 0.1, 8.6 ± 0.2, 16.9 ± 0.5, 5.9 ± 0.2, 7.3 ± 0.1 and 9.7 ± 0.7 μM, respectively. Specifically, the anti-tumor activity assays in vivo found that the inhibitory rates are 23.24 % for 1a, 61.27 % for 1alip, 76.06 % for 1aTlip. It is obvious that the targeted liposomes entrapped iridium(III) compound greatly enhance anti-cancer efficacy. Additionally, 1alip, 1blip and 1clip or targeted 1aTlip, 1bTlip and 1cTlip can effectively restrain the cell colony and proliferation in the G0/G1 period. 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip can increase reactive oxygen species (ROS) concentration, arouse a decline in the mitochondrial membrane potential and promote Ca 2+ release. RNA-sequence was applied to examine the signaling pathways. Taken together, the liposomes or targeted liposomes encapsulated compounds trigger cell death by way of apoptosis, autophagy, ferroptosis, disruption of mitochondrial function and PI3K/AKT/mTOR signaling pathways.
Competing Interests: Declaration of competing interest Authors declare no competing interest exists.
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Databáze: MEDLINE
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